The Developmental Therapeutics (DT) Research Program is a long-standing research program, established in 1974 as the first research program of the Yale Cancer Center (YCC). This program has 48 members representing 15 departments. The DT program has three main program goals: 1. To identify and characterize key molecular targets and therapeutic strategies for treatment of cancer and cancer-associated viral disease; 2. To foster and facilitate interactions between basic and clinical investigators interested in drug development; and 3. To translate YCC discoveries and science into the clinic using clinical trials which explore prognostic, predictive and pharmacodynamic biomarkers. This program has been highly successful in developing therapeutics as illustrated by considering a snapshot of recent scientific accomplishments. In work initiated during the previous grant period, twenty-five molecules have been discovered by DT members; 18 have been licensed to the pharmaceutical industry; 9 are undergoing preclinical testing; and 6 anticancer agents are in clinical testing in Phase I, II, and III trials. This includes carfilzomib that received FDA approval in July 2012 that was developed in the lab of Craig Crews in the previous grant period. The new leaders of the DT Program are Karen S. Anderson, PhD and Roy S. Herbst, MD, PhD, with basic science and clinical/translational expertise in structure-based drug design/drug discovery and translational research, personalized cancer therapies, and clinical trials. Dr. Anderson's primary role is to foster basic science clinical partnerships and facilitate the translation of basic science discoveries to preclinical studies. Dr. Herbst's role is to promote translational and clinical programs. This includes building multi-investigator teams comprised of basic, clinical, and population scientists assembled as tumor-type working groups that are focused on the various types of cancer. In addition, we recruited Dr. Paul Eder to lead the Phase I, DT effort. Under this new leadership, more molecules will enter trials at Yale in the future. The cancer-focused research of DT members has significantly benefited from YCC pilot grant funding. Since the last submission, $855,727 in YCC pilot funds have yielded over $8.4 million in extramural funding including 1 ROI and 1 P01 as well as 2 clinical trials. The funding in the DT program is quite robust with a total cancer-related funding of $16,693,963. Of this, over 80% is peer-reviewed ($13,233,968) and $4,240,718 ($2.8 direct costs) is from NCI. During the previous grant period (2006-11), members of this program published 397 cancer-related papers. This includes 179 that were collaborative, of which 42% were inter-programmatic and 9% were intraprogrammatic.